Helminth coinfections mitigate clinical, parasitological, and immune outcomes in Mozambican children with malaria.

Abstract

Clearance of Plasmodium falciparum infection requires a T_H1 immune response with production of pro-inflammatory cytokines, IgG1, and IgG3 responses. In contrast, infections with helminths are dominated by T_H2/T_reg immune responses characterized by production of anti-inflammatory cytokines, IgE, and IgG4, which could potentially interfere with malaria outcomes and immune responses. We recruited 441 malaria-symptomatic children aged 2-10 years attending two hospitals in the Manhiça District (Mozambique) and assessed infection by rapid antigen diagnostic test, microscopy, and/or quantitative PCR. Using Luminex, we measured concentrations of 30 cytokines and IgA, IgM, IgE, IgG, and IgG1-4 levels against 12 P. falciparum antigens and total IgE. Among 74 children diagnosed with malaria, 22% (16) were coinfected with STH, and 78% (58) had only P. falciparum. Soil-transmitted helminths (STH) coinfection associated with lower P. falciparum density (P = 0.005) and fever (P = 0.047). Coinfected children also had lower concentrations of plasma pro-inflammatory (IL-8, TNF, IFNα, IP-10, MCP1, MIG, MIP1β, and GM-CSF) and anti-inflammatory cytokines (IL-5, IL-10) (P < 0.05). Furthermore, antibody responses to a set of P. falciparum antigens, including SSP2 (IgG1, IgG4, IgG), PTRAMP (IgG3), MSP3 (IgG), RH5 (IgG1), and α-gal (IgG1), as well as total IgE, were elevated in STH coinfected children (P < 0.05). STH infections were associated with decreased P. falciparum parasitemia, downregulation of inflammatory cytokines, and enhanced antibody responses, potentially resulting in milder malaria episodes, suggesting enhanced protective immunity.